Influence of Bupropion on the Effects of MDMA

Phase 1

Completed

• Conditions: Healthy; Substance-related Disorders
• Interventions: Drug: MDMA; Drug: Bupropion; Drug: Placebo

• Registration Number: NCT01771874
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

The purpose of this study is to determinate the effect of a pre-treatment with bupropion, a dopamine and norepinephrine transporter inhibitor, on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"). The study will provide further understanding of the dopaminergic regulation of mood.

Detailed Description

3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is widely used by young people for its euphoric effects. MDMA releases serotonin (5-HT), dopamine (DA), and norepinephrine (NE). 5-HT release mainly contributes to the subjective effects of MDMA whereas NE release is involved in the cardiovascular and psychostimulant effects of MDMA. DA mediates the reinforcing addiction-related effects of drugs of abuse but it is unclear whether DA contributes to the acute effects of MDMA in humans. To determine the role of DA transporter-mediated DA release in the acute response to MDMA in humans the investigators test the effects of the DA transporter inhibitor bupropion on the physiological and subjective effects of MDMA. The investigators use a randomized double-blind placebo-controlled cross-over design with four experimental sessions. Bupropion or placebo will be administered before MDMA or placebo to 16 healthy volunteers. Subjective and cardiovascular responses will be repeatedly assessed throughout the experiments and plasma samples are collected for pharmacokinetics. The primary hypothesis is that bupropion reduces the MDMA-induced increase in positive mood.

Study Timeline

• Study First Submitted: 2012-10-24
• Study Start: 2013-01
• Study First Submitted QC: 2013-01-16
• Study First Posted: 2013-01-18
• Primary Completion: 2013-05
• Study Completion: 2013-09
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-20
• Last Update Posted: 2016-01-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Age between 18 and 45
• Understanding of the German language
• Subjects understand the procedures and the risks associated with the study
• Participants must be willing to adhere to the protocol and sign the consent form
• Participants must be willing to adhere to the protocol and sign the consent form
• Participants must be willing to drink only alcohol-free liquids and no xanthine-containing products(such as coffee, black or green tea, red bull, chocolate) after midnight of the evening before the study session, as well as during the study day
• Participants must be willing not to drive a traffic vehicle within 48 h following MDMA administration
• Women of childbearing potential must have a negative pregnancy test at the beginning of the study and must agree to use an effective form of birth control. Pregnancy tests are repeated before each study session
• Body mass index: 18-27 kg/m2

Exclusion Criteria

• Chronic or acute medical condition including clinically relevant abnormality in physical exam, laboratory values, or ECG. In particular: Hypertension (>140/90 mmHg) or Hypotension (SBP<85 mmHg). Personal or first-grade history of seizures. Cardiac or neurological disorder
• Current or previous psychotic or major affective disorder
• Psychotic or major affective disorder in first-degree relatives
• Prior illicit drug use (except tetrahydrocannabinol (THC)-containing products) more than 5 times or any time within the previous 2 months
• Pregnant or nursing women
• Participation in another clinical trial (currently or within the last 30 days)
• Use of medications that are contraindicated or otherwise interfere with the effects of the study medications (monoamine oxidase inhibitors, antidepressants, sedatives etc.)
• Tobacco smoking

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MDMA, bupropion, placebo	MDMA	Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two (actually 4) treatment conditions in the same subject. The four treatment conditions are placebo-placebo, bupropion-placebo, placebo-MDMA, and bupropion-MDMA.
MDMA, bupropion, placebo	Placebo	Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two (actually 4) treatment conditions in the same subject. The four treatment conditions are placebo-placebo, bupropion-placebo, placebo-MDMA, and bupropion-MDMA.
MDMA, bupropion, placebo	Bupropion	Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two (actually 4) treatment conditions in the same subject. The four treatment conditions are placebo-placebo, bupropion-placebo, placebo-MDMA, and bupropion-MDMA.

Primary Outcome Measures

Name	Time	Method
Positive Mood Effects	24 hours	A significant reduction of the (100-mm Visual Analog Scale) positive mood response to MDMA by bupropion.

Secondary Outcome Measures

Name	Time	Method
Heart rate (bpm)	10 hours
Body temperature	10 hours
Neuroendocrine plasma levels	10 hours	assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone
Drug plasma levels	24 hours	The plasma concentration of MDMA and bupropion is repetitively assessed
Blood pressure(mmHg)during 10 hours	10 hours
Effects on social cognition (emotion recognition and empathy)	10 hours
Influence of genetic cytochrome P450 2D6 polymorphisms on the metabolism of MDMA	24hours	We will assess the effects of the subjects' genotype and phenotype on MDMA and its metabolites plasma concentrations.

Trial Locations

Locations (1)

University Hospital Basel; 🇨🇭 Basel, Basel-Stadt, Switzerland